Whittaker RG, Herrmann DN, Bansagi B, Hasan BA, Lofra RM, Logigian EL, Sowden JE, Almodovar JL, Littleton JT, Zuchner S, Horvath R, Lochmüller H
Neurology (epub ahead of print), October 2015
Objectives: To describe the clinical and electrophysiologic features of synaptotagmin II (SYT2) mutations, a novel neuromuscular syndrome characterized by foot deformities and fatigable ocular and lower limb weakness, and the response to modulators of acetylcholine release.
Methods: We performed detailed clinical and neurophysiologic assessment in 2 multigenerational families with dominant SYT2 mutations (c.920T.G [p.Asp307Ala] and c.923G.A [p.Pro308-Leu]). Serial clinical and electrophysiologic assessments were performed in members of one family treated first with pyridostigmine and then with 3,4-diaminopyridine.
Results: Electrophysiologic testing revealed features indicative of a presynaptic deficit in neurotransmitter release with posttetanic potentiation lasting up to 60 minutes. Treatment with 3,4- diaminopyridine produced both a clinical benefit and an improvement in neuromuscular transmission.
Conclusion: SYT2 mutations cause a novel and potentially treatable complex presynaptic congenital myasthenic syndrome characterized by motor neuropathy causing lower limb wasting and foot deformities, with reflex potentiation following exercise and a uniquely prolonged period of posttetanic potentiation.